Pharmacological approach to diabetic macular edema.

Diabetic macular edema (DME) is a highly prevalent cause of vision loss and has a remarkable impact on public health, and on the quality of life of diabetic patients. Even though laser photocoagulation has been the standard of care for decades, a substantial group of patients are unresponsive and fail to improve after laser treatment. Recently, new pharmacological approaches based on the use of intravitreal drugs, such as corticosteroids and anti-vascular endothelial growth factor, have revolutionized the treatment of DME. The use of intravitreal drugs is supported by the improvement in visual acuity reported by several clinical trials and can limit the potentially destructive effects of the laser treatment. Encouraging results also emerged from studies evaluating the use of a combination therapy, or the association of intravitreal drugs and laser treatment. This review aims at providing a brief synopsis of the main investigations regarding the current pharmacological approach to DME.

Evidence for anti-VEGF treatment of diabetic macular edema.

Diabetic macular edema (DME) is the most important cause of vision loss in patients with diabetes mellitus. Diabetic retinopathy has a remarkable impact on public health and on the quality of life of diabetic patients and thus requires special consideration. The first line of treatment remains the management of systemic risk factors but is often insufficient in controlling DME and currently, laser retinal photocoagulation is considered the standard of care. However, laser treatment reduces the risk of moderate visual loss by approximately 50% without guaranteeing remarkable effects on visual improvement. For these reasons, new strategies in the treatment of DME have been studied, in particular the use of anti-vascular endothelial growth factor (anti-VEGF) drugs. VEGF is a pluripotent growth factor that acts as a vasopermeability factor and an endothelial cell mitogen. For this reason, it represents an interesting candidate as a therapeutic target for the treatment of DME. The aim of this article is to review the evidence behind the use of anti-VEGF drugs in the treatment of DME.

Steroids as part of combination treatment: the future for the management of macular edema?

Diabetic macular edema (DME), defined as a retinal thickening involving or approaching the center of the macula, plays a major role in vision loss related to diabetic retinopathy. This article presents an in-depth analysis of therapeutic perspectives on DME by means of an approach based on combination therapy with steroids. Corticosteroid drugs have been demonstrated to both inhibit the expression of vascular endothelial growth factor (VEGF) and the VEGF gene, and to have antiinflammatory properties. A treatment algorithm is provided regarding the management of DME. While grid laser photocoagulation remains the first-line therapy for focal vasogenic DME, diffuse DME can be effectively treated by means of intravitreal injections of corticosteroids. Recalcitrant DME can also be managed beneficially with intravitreal steroids. The management of DME is complex, and often multiple treatment approaches are needed. Each form of DME should be properly classified and specifically treated. The combination treatment has still an important role in the combined treatment options for DME.

Recurrence of hemispheric retinal vein occlusion.

The purpose of this article is to report a case in which a double hemispheric retinal vein occlusion (HSRVO) occurred in the same eye, involving firstly the superior half and later the inferior half of the retina. A 63-year-old woman with ill-controlled hypertension had been diagnosed with central retinal vein occlusion in the right eye in January 1998. The patient had a HSRVO of the superior hemiretina in November 2003, and a HSRVO of the inferior hemiretina in August 2005. The patient underwent a complete work-up, but the only detected risk factor was hypertension. Bearing in mind the absence of an effective treatment able to reduce both the incidence and the recurrence of retinal vein occlusion, detection and control of the risk factors, such as hypertension, is essential. We should make every effort to improve the compliance of our patients in controlling general diseases all their lives.

Choroidal excavation in choroidal osteoma complicated by choroidal neovascularization.

PurposeTo describe multimodal imaging features of choroidal osteoma (CO) complicated by choroidal neovascularization (CNV) and focal choroidal excavation (FCE).MethodsPatients presenting with CO and CNV between January and October 2016 were considered for this study. Diagnosis of CO was confirmed by ultrasound examination. All patients underwent multimodal imaging including optical coherence tomography (OCT), swept-source OCT angiography (DRI OCT Triton, Topcon, Inc., Tokyo, Japan) and fluorescein angiography (Spectralis HRA+OCT; Heidelberg Engineering, Heidelberg, Germany).ResultsTwo patients (one with bilateral CO) were included in the study. OCT showed a FCE in two eyes of two patients (one in correspondence of the CNV and the other adjacent to the CNV). OCT-A demonstrated presence of microvascular flow within neovascular network of the CNVs. Decalcification of the tumor was noted in correspondence of one eye with FCE.ConclusionsFCE may be found in eyes with choroidal osteoma and CNV. OCT-A was a valuable tool for detection of CNV complicating choroidal osteoma. Decalcification of choroidal osteoma may represent a common pathogenic pathway for development of FCE and CNV in choroidal osteoma.

Optical coherence tomography analysis of evolution of Bruch's membrane features in angioid streaks.

PurposeTo describe optical coherence tomography (OCT) features in the Bruch's membrane (BM) of eyes with angioid streaks (AS) and evaluate their evolution over the follow-up.Patients and methodsPatients with AS presenting between March 2016 and September 2016 at two tertiary referral centers were consecutively recruited in this study. Eligibility criteria included prior spectral domain (SD)-OCT images, taken at least 3 months before at the same referral center, with automated eye tracking and image alignment modules. Alterations of BM were described and compared to previous scans over the follow-up. Multimodal imaging was used to identify alteration of retinal pigment epithelium (RPE) and choroid.ResultsThirty-two eyes of 16 consecutive patients with AS were included. BM undulations, mostly observed around the optic nerve head, were found in 19 (59.4%) of 32 eyes. BM breaks were found in 31 (96.9%) out of 32 eyes. Evolution of BM undulations into BM breaks was observed in 5 eyes (15.6%). Choroidal neovascularization (CNV) was observed in 12 eyes (37.5%) during follow-up, typically in areas of BM interruption.ConclusionsBM undulations, probably caused by high stretching forces exerted on the BM around the optic nerve head, seem to precede some BM breaks. BM interruptions may be a preferred way for the growth of CNV, which was identified in one-third of our cases.

Visual representation of space in congenital and acquired strabismus.

The aim of the present work was to readdress the problem of altered spatial localization in strabismic subjects and to assess whether and how spatial representation is affected by the degree of plasticity of the brain. We therefore compared targeting performance in adult subjects affected by acquired strabismus versus children affected by congenital strabismus. Our data confirm the correlation between deviation of the eye and targeting errors, but they also show that this correlation is not present when strabismus occurs early in life. We suggest that the neuronal machinery involved in the building of an internal representation of space reaches its full maturity several years after birth and that this might explain the limited differences observed in targeting errors between normal and strabismic children.

Vascularized pigment epithelial detachment in adult-onset foveomacular vitelliform dystrophy.

PURPOSE: To report a case showing adult-onset foveomacular vitelliform dystrophy (AOFVD), associated with vascularized pigment epithelial detachment. CASE REPORT: A 72-year-old female affected by AOFVD complained with blurred vision and metamorphopsia in her right eye, seven months after a routinary clinical examination. Visual acuity in right eye dropped from 0.6 to 0.3, and biomicroscopic fundus examination revealed a serous pigment epithelial detachment arising from the temporal margin of the pseudovitelliform lesion. Fluorescein angiography showed an uneven filling of the pigment epithelial detachment, suggesting the presence of a subfoveal choroidal neovascularisation, which was confirmed by indocyanine green angiography. DISCUSSION: The association between AOFVD and vascularized pigment epithelial detachment, supports the hypothesis that AOFVD may be a different subgroup of age-related macular degeneration with specific genetic predisposition.

Subretinal fluid ferning test in rhegmatogenous retinal detachment.

PURPOSE: The ferning test involves a process of crystallization achieved simply by removing water and is feasible for all ocular fluids. The ferning test of subretinal fluid (SRF) from patients with rhegmatogenous retinal detachment (RRD) reveals three different patterns: type 1 showing thin crystals, type 2 with larger crystals and type 3 with small, curvilinear structures with no tree-like appearance. The present study was designed to determine whether the SRF ferning test is correlated with the clinical features and the surgical outcome of RRD. METHODS: A series of 65 consecutive patients with RRD at the first onset were considered. Particular attention was paid to duration, extension, and surgical outcome of RRD. SRF samples were collected during scleral buckling surgery. The fluid was dropped onto the slide of a light microscope, left to dry, and examined under the microscope. RESULTS: There was a significant difference between SRF ferning types 1 and 2 as regards, duration and extension (both p < 0.001). There was also a significant difference between SRF ferning types 2 and 3 as regards duration (p<0.001), extension (p<0.001), and surgical outcome (p<0.05). CONCLUSIONS: The ferning test of SRF is quick and simple and can be regarded as a useful tool for obtaining information about clinical features, such as duration or extension of first, onset in uncomplicated cases of RRD especially for purposes of forensic medicine.

Branch retinal vein occlusion and exudative retinal detachment: pathogenetical aspects.

Exudative retinal detachment (ERD) is an uncommon complication of branch retinal vein occlusion (BRVO). The ERD pathogenesis has been mainly related to the haemodynamic overload and to an impairment in the function of the retinal pigment epithelium. Data relative to 98 cases of BRVO without ERD were compared with the correspondent data of 10 cases of BRVO with ERD. Venous leakage showed a substantial equivalency between the two groups, while evaluation of retinal venous collaterals demonstrated a lower amount in the BRVO cases with ERD, with a statistically significant difference. Moreover, considering the various ERD localizations, we suggest that the ERD pathogenesis is mainly ascribable to the scant development of retinal venous collaterals but that an important role may also be played by the retinal pigment epithelium impairment consequent to the retinal ischaemia.

Cup/disk ratio in branch retinal vein occlusion.

Recent reports have been attempted to evaluate, without obtaining a positive result, whether the reduction in size of the optic disc may influence the pathogenesis of central retinal vein occlusion. Cup/disc ratios in the fellow eye of 67 patients with branch retinal vein occlusion were compared with the ratios of 67 controls matched to cases for age, sex and refractive defect. There was no significant difference between cup/disc ratios of the two groups. These results suggest that the anatomical features of the optic disc are of no importance in the development of branch retinal vein occlusion.

Exudative retinal detachment subsequent to retinal vein occlusion.

Previous studies have shown the possible development of exudative retinal detachment (ERD) as a complication of retinal vein occlusion (RVO). Considering 473 consecutive cases of RVO, only 3 cases of ERD with peculiar clinical aspects were discovered. In the first case, the ERD followed a branch RVO, but it developed in the opposite quadrant, with a late occurrence of venous retinal collaterals. In the second case, the ERD developed after a central RVO, having a retinoschisis aspect, with the subsequent occurrence of optic disk collateral vessels. In the third case, the ERD was secondary to a hemicentral RVO and involved the entire macular area. The pathogenesis of the ERD subsequent to RVO is still debated. Our experience seems to indicate that the ERD pathogenesis is linked not only to an inability of the draining vascular system, but also to an impairment in the function of the retinal pigment epithelium.

Ocular fluid ferning test and fractals.

The ferning test can be regarded as a crystallization process obtained by simple water subtraction. Such a process is feasible for every kind of ocular fluid (i.e. tears and aqueous, vitreous and subretinal fluids). The ferning test can be described in terms of fractal geometry, as the image characteristics related to this test are consistent with three of the main properties of fractals: self-similarity, fractal dimension and lacunarity.

Angiographic pattern of recurrent choroidal neovascularization in age-related macular degeneration.

PURPOSE: To evaluate the angiographic characteristics of recurrent choroidal neovascularization (R-CNV) in age-related macular degeneration (AMD). METHODS: A prospective investigation on 107 consecutive patients with exudative AMD and CNV not involving the fovea was conducted. Fluorescein angiography (FA) and indocyanine green angiography (ICGA) were planned before krypton laser treatment, and after 3 weeks, 2, 3, 4, 6, 9, 12, 18, and 24 months from photocoagulation. Laser treatment was FA-guided in eyes with classic CNV, and ICGA-guided in eyes with occult CNV on FA. RESULTS: At baseline on FA, 23.3% had classic CNV, whereas, 76.6% showed occult CNV. On ICGA, CNV assumed a focal and a plaque pattern in 81.3 and 18.6% of cases, respectively. Overall, post-laser CNVs occurred in 56 eyes. FA identified well-defined and ill-defined R-CNV in 25 and 75% of cases, respectively. ICGA identified three different R-CNV patterns: focal, annular, and plaque. Focal R-CNV was defined as a single dot-like hyperfluorescence, which was detected in 69.6% of cases, with subfoveal location in half of them. Annular R-CNV was identified by a hyperfluorescent lesion, partially or completely encircling treated area, which was visible in 19.6% of cases, all with subfoveal involvement. Plaque R-CNV was defined as a hyperfluorescent lesion larger than 1 disc diameter in size, and was seen in 10.7% of cases, all with subfoveal location. CONCLUSIONS: ICGA is able to improve R-CNV visualization identifying three different R-CNV patterns. Focal R-CNV is the most frequent pattern and can be re-treated in half of the cases.

Capillary macroaneurysms in central retinal vein occlusion.

The occurrence of macroaneurysms as a consequence of central retinal vein occlusion was previously reported in one study only with the appearance of a single capillary macroaneurysm. We report a case of central retinal vein occlusion presenting several capillary macroaneurysms. It may be supposed that retinal ischemia plays an important role in the pathogenesis of capillary macroaneurysms, in association with the pressure increase in the capillary network due to venous obstruction.

Primary empty sella syndrome and central retinal vein occlusion.

Empty sella syndrome (ESS) is a peculiar disease that may involve systemic, neurological or ophthalmological symptoms. Our report presents a case of primary ESS complicated with central retinal vein occlusion. In an attempt to explain the pathogenesis of the retinal venous stasis, it may be hypothesized that the compression of the optic nerve may produce a slowing of axoplasmic flow, with a consequent optic nerve head swelling. Thus the central retinal vein gets compressed with the clinical result of a retinal venous stasis.

Benign adenoma of the iris pigment epithelium: clinical and iris fluorescein angiographic features.

Benign adenoma of iris pigment epithelium is a rare neoformation characterized by a multinodular, dark brown to dark black, relatively stationary lesion, especially localized in the peripheral iris. We report a case of iris pigment epithelium adenoma with no evidence of change during the 6-year follow-up. Iris fluorescein angiography showed a mild staining of the lesion without evidence of abnormal vessels. The importance of fluorescence iridography in the differential diagnosis of iris-pigmented lesions is discussed.

Grid laser treatment of macular edema in macular branch retinal vein occlusion.

AIM: Macular branch retinal vein occlusion (MBRVO) is a subgroup of branch retinal vein occlusion in which the occlusion is limited to a small venous vessel draining a sector of the macular region. The present study aims to evaluate the efficacy of grid laser treatment for macular edema in MBRVO. METHODS: 77 Patients with MBRVO of recent onset were prospectively studied during a 24 month period. Eyes were randomly assigned to a grid laser treatment group and to a control group. Clinical parameters such as visual acuity, presence of macular edema and angiographic features were recorded during the follow-up period. RESULTS: Visual acuity increased significantly in both groups after 3 months of follow-up (p<0.001) and after 1 year of follow-up (p<0.005). No additional improvement was noted at the two year control. There was no statistical difference between the two groups. CONCLUSIONS: The visual prognosis of MBRVO is not improved after grid laser treatment of macular edema. This suggests that sudden ischemic damage to central photoreceptors rather than macular edema is the main factor for permanent visual acuity reduction.